Nonpathogenic common variants of IFNGR1 and IFNGR2 in association with total serum IgE levels

Atopy is an immune disorder in which a Th2 dominant mechanism leads to high IgE levels and the clinical disorder asthma. It has been postulated that the Th1 cytokine IFN gamma, acting through its heterodimeric receptors, IFN gamma R1 and IFN gamma R2, in the induction/ proliferation of Th1 cells, might suppress the Th2 responses that may underlie atopic asthma. However, neither murine nor human variants of IFN gamma associate with atopy. Several dysfunctional mutations have been identified in IFN gamma receptor genes (IFNGR1 and IFNGR2) in relation to severe and selective infections with poorly pathogenic organisms. However, little is known about common polymorphisms and their functional role in atopy. To test whether such variants of IFNGR1 and IFNGR2 relate to atopic asthma, we conducted a genetic association study in both British (n = 300) and Japanese (n = 200) populations. An intronic variant of IFNGR1 showed marginal association with total serum IgE levels in the British population compared with those with total IgE levels <30 IU/ml and those with >120-500 IU/ml [odds ratio = 2.00 (95% CI 1.00-4.07), P = 0.048]. A coding variant, Gln64Arg of the IFNGR2, also associated with total serum IgE levels in the British population [chi(2) = 5.08, P = 0.024], Further genetic and functional analyses are needed to clarify the role of variants of IFN gamma receptor genes in atopic immune disorder among different ethnic groups. (C) 1999 Academic Press.